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Structural highlights

Disease

AKT3_HUMAN Hemimegalencephaly;Megalencephaly-polymicrogyria-postaxial polydactyly-hydrocephalus syndrome. AKT3 is a key modulator of several tumors like melanoma, glioma and ovarian cancer. Active AKT3 increases progressively during melanoma tumor progression with highest levels present in advanced-stage metastatic melanomas. Promotes melanoma tumorigenesis by decreasing apoptosis. Plays a key role in the genesis of ovarian cancers through modulation of G2/M phase transition. With AKT2, plays a pivotal role in the biology of glioblastoma. The disease is caused by variants affecting the gene represented in this entry.

Function

AKT3_HUMAN AKT3 is one of 3 closely related serine/threonine-protein kinases (AKT1, AKT2 and AKT3) called the AKT kinase, and which regulate many processes including metabolism, proliferation, cell survival, growth and angiogenesis. This is mediated through serine and/or threonine phosphorylation of a range of downstream substrates. Over 100 substrate candidates have been reported so far, but for most of them, no isoform specificity has been reported. AKT3 is the least studied AKT isoform. It plays an important role in brain development and is crucial for the viability of malignant glioma cells. AKT3 isoform may also be the key molecule in up-regulation and down-regulation of MMP13 via IL13. Required for the coordination of mitochondrial biogenesis with growth factor-induced increases in cellular energy demands. Down-regulation by RNA interference reduces the expression of the phosphorylated form of BAD, resulting in the induction of caspase-dependent apoptosis.^{[1] [2]}

References

1. ↑ Wright GL, Maroulakou IG, Eldridge J, Liby TL, Sridharan V, Tsichlis PN, Muise-Helmericks RC. VEGF stimulation of mitochondrial biogenesis: requirement of AKT3 kinase. FASEB J. 2008 Sep;22(9):3264-75. PMID:18524868 doi:10.1096/fj.08-106468
2. ↑ Moriya C, Jinnin M, Yamane K, Maruo K, Muchemwa FC, Igata T, Makino T, Fukushima S, Ihn H. Expression of matrix metalloproteinase-13 is controlled by IL-13 via PI3K/Akt3 and PKC-δ in normal human dermal fibroblasts. J Invest Dermatol. 2011 Mar;131(3):655-61. PMID:21191416 doi:10.1038/jid.2010.361